The Importance of Anti-anaerobic Therapy for Acute Pelvic Inflammatory Disease (PID)

• ClinicalTrials.gov Identifier: NCT01160640
• Recruitment Status: Completed
• First Posted: July 12, 2010
• Results First Posted: December 21, 2016
• Last Update Posted: July 10, 2018
• Sponsor: Harold Wiesenfeld
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): Harold Wiesenfeld, University of Pittsburgh

Study Description

Brief Summary:

This study is a randomized placebo-controlled trial comparing two antibiotic treatment regimens for acute PID. Women with acute PID will be randomized to one of two treatment regimens: 1) a single intramuscular dose of ceftriaxone 250 mg, doxycycline 100 mg orally twice a day for 14 days, along with placebo tablets orally twice a day for 14 days or 2) same doses of ceftriaxone and doxycycline, and metronidazole 500 mg orally twice a day for 14 days. The primary objective is to compare the eradication of anaerobic organisms from the upper genital tract between women who receive standard outpatient antibiotic treatment to those who receive standard outpatient treatment along with a two-week course of metronidazole.

Condition or disease	Intervention/treatment	Phase
Pelvic Inflammatory Disease	Drug: Ceftriaxone; Drug: Doxycycline; Drug: Metronidazole; Drug: Placebo Oral Capsule	Phase 2

Detailed Description:

This study is a randomized placebo-controlled trial comparing two antibiotic treatment regimens for acute PID. Women with acute PID will be randomized to one of two treatment regimens. One group of women will receive a single intramuscular dose of ceftriaxone 250 mg, doxycycline 100 mg orally twice a day for 14 days, along with placebo tablets orally twice a day for 14 days. The second group of women will receive the same doses of ceftriaxone and doxycycline, and metronidazole 500 mg orally twice a day for 14 days. The primary objective is to compare the eradication of anaerobic organisms from the upper genital tract in women with acute PID who receive standard outpatient antibiotic treatment to the eradication of these organisms from the upper genital tract in women who receive standard outpatient treatment along with a two-week course of metronidazole. Women will be followed for one month for clinical outcomes, and will undergo assessment for clearance of microorganisms from the upper genital tract. Our hypothesis is that an antibiotic treatment regimen that includes anaerobic coverage will more effectively clear anaerobic organisms from the endometrium in women with acute PID compared to a standard antibiotic treatment regimen lacking effective antibiotic coverage against anaerobes.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 233 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Importance of Anti-anaerobic Therapy for Acute PID
• Study Start Date: November 2010
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: August 2015

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Ceftriaxone/Doxycycline/Placebo Oral Cap; ceftrixone 250mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus placebo oral capsule PO bid x 14 days	Drug: Ceftriaxone; ceftrixone 250mg IM single dose; Other Name: Rocephin; Drug: Doxycycline; Doxycycline 100 mg PO bid x 14 days; Drug: Placebo Oral Capsule; placebo oral capsule PO bid x 14 days
Active Comparator: Ceftriaxone, Doxycycline, Metronidazole; ceftriaxone 250 mg IM single dose plus doxycycline 100 mg PO bid x 14 days plus metronidazole 500 mg PO bid x 14 days	Drug: Ceftriaxone; ceftrixone 250mg IM single dose; Other Name: Rocephin; Drug: Doxycycline; Doxycycline 100 mg PO bid x 14 days; Drug: Metronidazole; metronidazole 500 mg PO bid x 14 days; Other Name: Flagyl

Outcome Measures

Primary Outcome Measures :

1. Clearance of Anaerobic Organisms From the Endometrium [ Time Frame: Enrollment to 30 days ]
   Clearance of anaerobic microorganisms from the endometrium at the 30 day follow-up visit among women who had anaerobic microorganisms detected in their endometrial tissue sample at enrollment. Clearance is defined as no anaerobic microorganisms detected in the endometrial tissue biopsy sample collected at the 30-day visit.

Secondary Outcome Measures :

1. The Prevalence of M. Genitalium in the Cervix and Endometrium From Women With Acute PID. [ Time Frame: enrollment ]
   The number of women who had M. genitalium detected in cervical and endometrial biopsy cultures by nucleic acid amplification tests at enrollment.
2. The Eradication of M. Genitalium From the Lower and Upper Genital Tract Following Antibiotic Therapy for Acute PID. [ Time Frame: Enrollment to 30 days ]
   M. genitalium not detected in the cervical and endometrial cultures by nucleic acid amplification testing at the 30 day visit among women who had M. genitalium detected at either anatomical site at the enrollment visit.
3. Resolution of Clinical Signs and Symptoms of Acute PID - Intention to Treat Analysis [ Time Frame: Enrollment to 3 day follow up visit ]
   Clinical response to treatment is improvement (reduction) of the McCormack Scale total score from baseline to day 3 follow-up visit. Participants without a 3-day measure were considered treatment failures.
4. Identification of Endometrial Microorganisms Present Obtained From Women With or Without Evidence of Endometritis. [ Time Frame: enrollment ]
   Identification of endometrial microorganisms present obtained from women with or without evidence of endometritis using a combination of culture methods, rRna sequencing and whole genomic sequencing. The aim is to identify the etiology of endometritis.

Eligibility Criteria

• Ages Eligible for Study: 15 Years to 40 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Women must meet all of the following inclusion criteria:

1. Age 15-40 at the time of enrollment (Note: Participants between the ages of 15-17 will require written informed consent from parent/legal guardian. Written assent will also be obtained from the minor)

2. Acute PID, defined by symptoms and signs guided by current CDC guidelines:50

   1. Current symptoms of lower abdominal or pelvic pain (present for ≤30 days) AND
   2. Cervical motion tenderness AND/OR uterine tenderness AND/OR adnexal tenderness on pelvic examination
3. Ability to provide written informed consent

Exclusion Criteria:

Women with any of the following will be ineligible to participate:

1. Pregnant or nursing a baby (Note: a urine pregnancy test will be done at enrollment. Result must be negative to participate in the study.)
2. Uterine procedure (e.g. dilation and curettage, abortion) or miscarriage within the past 6 weeks.
3. Allergy to any of the study medications (cephalosporins, doxycycline, or metronidazole) or Type 1 hypersensitivity allergic reaction to penicillin for those with unknown tolerance to cephalosporins.
4. Systemic or vaginal antibiotic therapy in the preceding 7 days
5. Requires inpatient PID therapy (per the current CDC guidelines)50
6. Inability to obtain an endometrial biopsy at enrollment
7. Known inability to comply with the follow-up visits
8. Prior hysterectomy
9. Menopause (including natural menopause defined as lack of menses for 12 consecutive months [in the absence of pregnancy] and surgical menopause defined as a woman who has had both ovaries removed)
10. Inability to swallow pills
11. Not willing to refrain from alcohol during the two week treatment period (and two additional days following completion of study medication)
12. Other condition present at enrollment that requires additional antibiotic treatment

13. Current use of any of the following medications:

    • Anticoagulants, coumarin- or indandione-derivative: warfarin
    • cimetidine (Tagamet)
    • Disulfiram
    • Seizure medications including: phenytoin (Dilantin), carbamezapine (Tegretol), barbiturates (i.e. Phenobarbital)
    • Lithium
    • Immunosuppressive drugs including: cyclosporine, amprenavir
    • Antacids, minerals or bismuth subsalicylate (Pepto Bismol)
14. Any condition, in the opinion of the investigator that would interfere with the participant's safety or with study outcomes
15. Participation in any study involving an investigational product in the past 30 days or anticipation of participation in any study using an investigational product in the next 30 days
16. Previous participation in this study
17. Evidence of a tuboovarian abscess

Contacts and Locations

Locations

United States, Pennsylvania

Allegheny County Health Department Sexually Transmitted Diseases Clinic

Pittsburgh, Pennsylvania, United States, 15213

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, United States, 15213

UPMC Mercy Hospital

Pittsburgh, Pennsylvania, United States, 15219

Sponsors and Collaborators

Harold Wiesenfeld

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Harold C Wiesenfeld, MD; University of Pittsburgh

More Information

• Responsible Party: Harold Wiesenfeld, Associate Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT01160640
• Other Study ID Numbers: PRO10010112; 1U19AI084024-01 ( U.S. NIH Grant/Contract )
• First Posted: July 12, 2010
• Results First Posted: December 21, 2016
• Last Update Posted: July 10, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Harold Wiesenfeld, University of Pittsburgh:

PID; Pelvic Inflammatory Disease

Additional relevant MeSH terms:

Pelvic Inflammatory Disease; Pelvic Infection; Infection; Adnexal Diseases; Metronidazole; Doxycycline; Ceftriaxone; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials